EP1485625B1 - Radioisotope generator including one or more component supports - Google Patents

Radioisotope generator including one or more component supports Download PDF

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Publication number
EP1485625B1
EP1485625B1 EP02807104A EP02807104A EP1485625B1 EP 1485625 B1 EP1485625 B1 EP 1485625B1 EP 02807104 A EP02807104 A EP 02807104A EP 02807104 A EP02807104 A EP 02807104A EP 1485625 B1 EP1485625 B1 EP 1485625B1
Authority
EP
European Patent Office
Prior art keywords
plate
latching member
latching
generator
bracing
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP02807104A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP1485625A1 (en
Inventor
Mark Kinneir Dufort Limited TEUCHER
Philip Kinneir Dufort Limited WALSH
Terence Robert Frederick Forrest
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GE Healthcare Ltd
Original Assignee
GE Healthcare Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by GE Healthcare Ltd filed Critical GE Healthcare Ltd
Priority to SI200230912T priority Critical patent/SI1485625T1/sl
Publication of EP1485625A1 publication Critical patent/EP1485625A1/en
Application granted granted Critical
Publication of EP1485625B1 publication Critical patent/EP1485625B1/en
Priority to CY20101100685T priority patent/CY1110674T1/el
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G1/00—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
    • G21G1/04—Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes outside nuclear reactors or particle accelerators
    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G4/00—Radioactive sources
    • G21G4/04—Radioactive sources other than neutron sources
    • G21G4/06—Radioactive sources other than neutron sources characterised by constructional features
    • G21G4/08—Radioactive sources other than neutron sources characterised by constructional features specially adapted for medical application

Definitions

  • the present invention relates to a radioisotope generator comprising an interengaging component support , the radioisotope generator being of the type commonly used to generate radioisotopes such as technetium-99m ( 99m Tc).
  • the radioisotope generator includes shielding around the ion exchange column containing the parent radioisotope along with means for eluting the daughter radioisotope from the column with an eluate, such as saline solution.
  • an eluate such as saline solution.
  • the eluate is passed through the ion exchange column and the daughter radioisotope is collected in solution with the eluate, to be used as required.
  • this radioisotope is the principle product of the radioactive decay of 99 Mo.
  • the 99 Mo is adsorbed on a bed of aluminium oxide and decays to generate 99m Tc.
  • the 99m Tc has a relatively short half-life it establishes a transient equilibrium within the ion exchange column after approximately twenty-four hours. Accordingly, the 99m Tc can be eluted daily from the ion exchange column by flushing a solution of chloride ions, i.e. sterile saline solution through the ion exchange column. This prompts an ion exchange reaction, in which the chloride ions displace 99m Tc but not 99 Mo.
  • the radioisotope generation process In the case of radio-pharmaceuticals, it is highly desirable for the radioisotope generation process to be performed under aseptic conditions i.e. there should be no ingress of bacteria into the generator. Moreover, due to the fact that the isotopes used and generated with the generator are radioactive, and are thereby extremely hazardous if not handled in the correct manner, the radioisotope generation process also should be conducted under radiologically safe conditions. Naturally, it is desirable to ensure that when the elution process is performed, the radiological safety of the generator is not compromised. In particular, when the eluate is introduced into the generator, it is important for the radiological safety of the generator to be maintained.
  • United States Patent No. 3,946,238 describes a shielded radioisotope generator comprising a cylindrical shielded housing for a central repository.
  • the repository is bound by a removable top cover and side walls and a base which are made from lead and which act as the shielding.
  • a bottle is located which contains an ion exchange column in which 99 Mo is absorbed.
  • the top cover is removed, and the saline is introduced by way of a transfer pipette.
  • the saline solution is introduced by means of the pipette to an annular region between the bottle and the inner surfaces of the shielding.
  • the saline solution flows in a controlled manner into the bottle containing the ion exchange bed via a series of radial openings in the wall of the bottle.
  • the transfer pipette has a long handle designed such that a user's hands always remain outside the generator when saline is introduced into the annular region about the bottle. It is apparent, however, that the removal of the top cover for the purposes of introducing the saline solution constitutes an unacceptable radiological risk as the interior of the repository is radioactive.
  • United States Patent No. 3,564,256 describes a radioisotope generator having quick-coupling members for the elution process.
  • the generator includes a cylindrical holder containing a radioactive substance bound to an ion exchange bed.
  • the holder is closed by rubber plugs at both ends, and is surrounded by shielding having passages opposite each of the rubber plugs in which respective needles are located.
  • quick-coupling members are provided to enable a syringe vessel containing a saline solution to be quickly and easily connected to one of the needles and to enable a collection vessel to be connected to the other of the two needles.
  • each one of the rubber plugs of the cylindrical holder is pierced by one of the needles to prompt the elution of 99m Tc from the ion exchange column.
  • Suitable quick-coupling members proposed in the document are conventional detachable injection needle to injection syringe connections.
  • United States Patent No. 4,387,303 describes a radioisotope generator comprising a column having an elute inlet aperture and an elute outlet aperture and containing an ion exchange bed with the parent radioisotope. Both the elute inlet and outlet are in communication with channels in the surrounding shielding. One of the channels, that is in communication with the elute outlet, is connected to a tapping point on the generator via an eluate conduit. The tapping point is adapted to receive an evacuated elution vial for collection of the daughter radioisotope in solution and consists of a hollow needle that pierces the seal to the evacuated elution vial.
  • the eluate conduit is also in communication with a source of sterile air and the generator includes a device for interrupting the elution process before the elution vial is filled by interrupting the flow of sterile air. No information is provided with regard to the construction of the generator and in particular no information is provided as to how the hollow needle at the tapping point is held in position.
  • the present invention seeks to provide a radioisotope generator comprising a component support, wherein the component support is simple in construction but provides greater reliability than existing simple component supports and so is particularly suited for use in radioisotope generators where there exists a need for a radioisotope generator that is simple in construction but which ensures the necessary degree of sterility and radiological protection.
  • a radioisotope generator including one or more component supports, wherein each component support comprises a latching member and a first plate on which said latching member is mounted, said latching member flexibly movable between an engaging position and an open position characterised in that said first plate includes an opening at or adjacent the latching member for receiving a bracing membersaid bracing member being mechanically associated with the latching member and adapted to prevent movement of the latching member to the flexed open position.
  • the opening in the first plate is preferably an aperture in the first plate adjacent the latching member on the side of the latching member facing the direction of movement of the latching member from the engaging position to the open position.
  • the opening is of non-circular cross-section and the bracing member has a corresponding non-circular cross-section.
  • the latching member may additionally include a camming surface engageable by the bracing member for urging the latching member away from the open position.
  • the component support may also include a second plate on which the bracing member is mounted, the second plate being arranged to lie substantially parallel to the first plate when the bracing member is inserted through the opening in the first plate.
  • the latching member is preferably a generally L-shaped structure consisting of a wall and a flange projecting therefrom, and in a preferred embodiment the latching member also includes a second flange arranged substantially parallel to the first flange for defining a slot therebetween. It is envisaged but by no means essential that the component support comprises at least two opposing latching members and respective bracing members.
  • the latching member of the generator may be mounted on a closure plate of the generator which includes an opening for receiving the bracing member, and wherein the bracing member is mounted on a cover plate of the generator such that insertion of the bracing member into the opening mounts the cover plate over the closure plate.
  • the radioisotope generator has two latching members mounted on the closure plate either side of a central component aperture and wherein the cover plate also includes a component aperture for alignment with the component aperture in the closure plate.
  • the radioisotope generator may also include a fluid port comprising a hollow generally cylindrical body and a retaining plate, the hollow body being received in the component apertures in the closure plate and the cover plate and the retaining plate being engaged by the opposed latching members for securely holding the fluid port in position.
  • the radioisotope generator includes a container consisting of a wall and a floor, with the opening to the container being closed by a closure plate.
  • the latching member is located on the container wall and the closure plate includes a bracket for engagement with the latching member and an opening at or adjacent the bracket and the bracing member is provided on a cover plate such that insertion of the bracing member into the opening in the closure plate aligns the bracing member with the latching member thereby to prevent movement of the latching member to the open position.
  • Figure 1 illustrates a component support for use in the radioisotope generator of the present invention
  • Figure 2 illustrates a radioisotope generator showings the location of supports for tapping spikes in accordance with the present invention.
  • the component support is illustrated generally by reference numeral 29, and the component illustrated in Figure 1 is a spike 1 which projects through an aperture 2 in a plate 3 and has a planar mounting member 4 that is held in position by a pair of latching members 5.
  • the latching members are movable between an engaging position in which they engage the planar mounting member and an open position in which the planar mounting member is not restrained by the latching members.
  • Each of the pair of latching members 5 includes a wall 6 projecting outwardly from the surface of the plate 3 (downwardly as illustrated in Figures 1 and 2 ).
  • the walls 6 are each spaced from the aperture 2 diametrically opposite one another across the aperture 2.
  • a flange 7 is provided at the free end of each wall 6.
  • the flanges 7 on each of the walls project away from the walls towards one another and extend substantially parallel to the plate 3.
  • a second flange 8, substantially parallel to the first flange 7, is provided between the first flange 7 and the plate 3.
  • the first 7 and second 8 flanges thus form a slot 9 suitable for receiving a planar member 4.
  • the plate 3 is preferably made from a hard plastics material and the walls 6 and flanges 7, 8 are preferably moulded as a single unit with the plate 3. This results in the walls 6 and flanges 7, 8 having a small degree of resiliency sufficient to be suitable for "snap-fit" engagement of a planar member within the slot 9 defined by the first 7 and second 8 flanges.
  • the first flange 7 has a camming surface 10 facing away from the plate 3 for guiding and centering a planar member 4 towards the slot 9 and for urging the small amount of flexure of the opposed walls 6 necessary to permit the planar member 4 to pass the periphery of the first flange 7 whereupon the walls 6 'snap' back into position with the planar member 4 located and held in the slot 9 between the first and second flanges 7, 8.
  • the component supports 29 illustrated in Figures 1 and 2 however provide a greatly improved reliability of securement over convention snap-fit connectors, which renders the component supports 29 particularly suited for use in radioisotope generators.
  • the component supports 29 include a cover 11 that is arranged to overlie the plate 3.
  • the cover 11 has a component aperture 12 for alignment with the aperture 2 in the plate 3.
  • the cover 11 also has a pair of bracing members 13 that project (downwardly in Figures 1 and 2 ) away from the cover 11. Also, adjacent each of the walls 6, on the opposite side of each of the walls 6 to the flanges 7, 8, respective brace apertures 14 are provided in the plate 3.
  • the bracing members 13 on the cover 11 are positioned either side of the component aperture 12 so as to be aligned with the brace apertures 14 in the plate 3.
  • the brace apertures 14 are sized to permit the passage of the bracing members 13 and preferably are non-circular in cross-section so that the bracing member 13 is keyed into the brace aperture 14.
  • each associated wall 6 and bracing member 13 have co-operable camming surfaces and followers.
  • the camming surface 15 is on the wall 6 facing towards the bracing member 13. This enables the bracing member 13 to actively engage with and urge the wall 6 inwardly towards the planar member 4 when inserted in the slot 9 defined by the first and second flanges 7, 8. This further improves the reliability of the securement of the component provided by the component supports 29.
  • Figure 2 illustrates the location of the component supports in a radioisotope generator 16.
  • the radioisotope generator 16 has an outer container 17, a closure plate, referred to herein as a top plate 3 which is sealingly secured to the outer container 17, and a separate top cover 11 which is secured to the outer container 17 over the top plate 3.
  • a radioactive shield 18 is located which is preferably, but not exclusively, made from either lead or a depleted uranium core within a stainless steel shell.
  • the radioactive shield 18 surrounds a tube 19 containing an ion exchange column 20.
  • the ion exchange column 20 preferably consists of a mixture of aluminium and silica, onto which molybdenum in the form of its radioactive isotope, 99 Mo is adsorbed.
  • the tube 19 containing the ion exchange column 20 has frangible rubber seals 21 and 22 at opposing ends 23 and 24 which, as illustrated, when in use are pierced by respective hollow needles 25 and 26.
  • Each of the hollow needles 25 and 26 are in fluid communication with respective fluid conduits 27, 28 which in turn are in respective fluid communication with an eluent inlet and an eluate outlet.
  • the fluid conduits 27, 28 are preferably flexible plastics tubing and in the case of the tubing 27 that communicates with the hollow needle 25 at the top 23 of the ion exchange column 20, the length of the tubing 27 is much greater than the minimum required to connect the hollow needle 25 with the eluent inlet.
  • the top plate 3 of the radioisotope generator 16 has a pair of apertures 2 through which the respective eluent inlet and eluate outlet components project.
  • the eluent inlet and eluate outlet components are each hollow spikes 1 though in the case of the inlet component the hollow spike additionally includes a filtered air inlet 30.
  • the hollow spike 1 consists of an elongate generally cylindrical spike body 31 and an annular retaining plate 32 which is attached to or is moulded as a single part with one end of the spike body 31.
  • the opposing end of the spike body 31 is shaped to a point and has an aperture 33 communicating with the interior of the spike body 31 adjacent the point.
  • This pointed end of the spike body 31 is shaped so that it is capable of piercing a sealing membrane of the type commonly found with sample vials.
  • the annular retaining plate 32 forms a skirt projecting outwardly from the spike body 31 and may be continuous around the spike body 31 or discontinuous in the form of a plurality of discrete projections.
  • the top cover 11 of the radioisotope generator 16 also includes a pair of apertures 12 arranged so as to align with the apertures 2 in the top plate 3 and shaped to allow through passage of the spike body 31.
  • each of the hollow spikes 1 is arranged to be held and supported by its annular retaining plate 32 by latching members 5 located on the inside of the top plate 3 whilst the hollow spike body 31 projects through the apertures in both the top plate 3 and the top cover 11 to the exterior of the outer container 17.
  • Each one of the apertures 12 in the top cover 11 is located at the bottom of a well 34 that is shaped to receive and support either an isotope collection vial 35 or a saline supply vial 36.
  • both vials 35, 36 are housed outside of the outer container 17 and are not exposed to radiation from the ion exchange column 20.
  • the hollow spikes 1 are held in place by the component supports 29 as described earlier with reference to Figure 1 .
  • the spike body 31 projects through the aligned apertures in the top plate 3 and the top cover 11 and is securely held in position by engagement of the annular retaining plate 32 in the slot 9 defined by the first and second flanges 7, 8 of the latching members 5. Retention of the plate 32 in the slot 9 is maintained by the supporting action of the bracing members 13 outside of the walls 6 of the latching members 5 which substantially prevent outward flexure of the walls 6.
  • the spike body 31 is inserted through the aperture 2 in the top plate 3 and the annular retaining plate 32 contacts the camming surfaces 10 on an opposing pair of first flanges 7. Further pressure applied to the retaining plate 32 forces outward flexure of the walls 6 supporting the first flanges 7 until the retaining plate 32 is able to pass the free end of the first flanges 7. Once the retaining plate 32 has passed the first flanges 7 the external pressure on the walls 6 is eased and the walls 6 'snap' back to their normal position locating the retaining plate 32 in the slots 9 defined by the first and second flanges 7 and 8.
  • the top cover 11 is then positioned over the top plate 3 with the apertures 12 in the top cover 11 aligned with the spike body 31 and the bracing members 13 aligned with apertures 2 in the top plate 3 adjacent each of the walls 6.
  • the bracing members 13 pass through the apertures 2 in the top plate 3 so as to be positioned next to, and preferably in contact with, the outer surfaces of the walls 6.
  • the interaction of the bracing members 13 on the top cover 11 and the walls 6 of the top plate 3 thus provide reliable securement of the retaining plate 32 of the hollow spike 1 in the slot 9 defined by the first and second flanges 7, 8.
  • the tubing 27 and 28 is then fluidly attached to the hollow spikes 1 and the outer container 17 is closed when the top plate 3 and the top cover 11 are secured to the container.
  • a user positions the frangible seal of the vial over the pointed end of the spike and pushes the vial down onto the spike 1. This causes the seal on the vial 35 or 36 to be pierced establishing fluid communication between the spike 1 and the vial. Once the seal has been pieced by the spike 1, the vial is pushed down over the spike 1 until it rests and is supported by the well 34 in the top cover 11.
  • saline solution 37 is drawn through the ion exchange column 20, by establishing a pressure differential across the ion exchange column 20. This is accomplished by connecting the saline supply vial 36 to the eluent inlet which is in fluid communication with the top end 23 of the ion exchange column 20 via the tubing 27 and hollow needle 25 and connecting an evacuated collection vial 35 to the eluate outlet which is in fluid communication with the bottom end 24 of the ion exchange column 20 via the tubing 28 and hollow needle 26.
  • the pressure differential is established by virtue of the fluid pressure of the saline in the supply vial 36 and the extremely low pressure in the evacuated collection vial 35. This urges passage of the saline solution 37 through the ion exchange column 20 to the collection vial 35 carrying with it the daughter radioisotope.
  • the component support is simple in design but by the interaction of the bracing member on one plate with the wall of the snap-fit component on the other plate and highly reliable component support is provided. Although reference has been made in the description to a component support suitable for a hollow spike, it will be apparent that the component support may be employed with alternative components that are intended to be secured in a snap-fit holder.
  • the component support may be used as a means for attaching the top plate to the outer container of the radioisotope generator.
  • latching members are attached to the inner side walls of the outer container.
  • Each latching member is spaced from the wall of the outer container by means of a bridge element so as to define a bracket receiving region between the latching member and the wall of the container.
  • the wall of the latching member is arranged substantially parallel to the container wall and the slot defined by the paired flanges mounted on the wall of the latching member lies substantially perpendicular to the container wall.
  • This arrangement also requires the top plate to have an equivalent number of brackets for location and engagement with respective latching members.
  • the bracket attached to the periphery of the top plate and projecting downwardly therefrom, engages the first of the flanges on the latching member.
  • the bracket urges the latching member to flex away from the container wall thereby enlarging the bracket receiving region until the bracket is capable of passing the periphery of the flange whereupon the latching member snaps back into position trapping part of the bracket in the slot defined by the two flanges.
  • the bracing member projects from the top cover and is locatable in an aperture in the top plate, such that, as before, it is mechanically associated with the latching member and acts to brace the latching member against flexure.
  • the bracing means is locatable through an aperture in the top plate such that it acts as an exterior abutment to the component support wall.
  • the component support wall may include a blind bore, into which the bracing means is inserted, to provide the desired improved support for the latching member.
  • the plates of the component support contain apertures through which the component passes.
  • the component may extend away from the surface of the first plate bearing the walls of the component support (in the illustrated embodiment the top plate 3) in which case the second plate (in the illustrated embodiment the top cover 11) need only align the bracing members with the brace apertures in the first plate.
  • paired flanges defining a slot are illustrated above, it will be appreciated that the slot may be defined between a single flange and the surface of the first plate. Further and alternative features of the component support are envisaged without departing from the scope of the present invention as claimed.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Radiation-Therapy Devices (AREA)
  • Nuclear Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Saccharide Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Supports For Pipes And Cables (AREA)
  • Snaps, Bayonet Connections, Set Pins, And Snap Rings (AREA)
  • Medicines Containing Plant Substances (AREA)
EP02807104A 2002-03-20 2002-12-11 Radioisotope generator including one or more component supports Expired - Lifetime EP1485625B1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
SI200230912T SI1485625T1 (sl) 2002-03-20 2002-12-11 Radioizotopni generator, ki vključuje enega ali več nosilcev sestava
CY20101100685T CY1110674T1 (el) 2002-03-20 2010-07-21 Γεννητρια ραδιοϊσοτοπων που περιλαμβανει ενα ή περισσοτερα στηριγματα εξαρτηματων

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0206550 2002-03-20
GB0206550A GB2386742B (en) 2002-03-20 2002-03-20 Radioisotope generator component support
PCT/GB2002/005624 WO2003081055A1 (en) 2002-03-20 2002-12-11 Component support and radioisotope generator including one or more component supports

Publications (2)

Publication Number Publication Date
EP1485625A1 EP1485625A1 (en) 2004-12-15
EP1485625B1 true EP1485625B1 (en) 2010-04-28

Family

ID=9933344

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02807104A Expired - Lifetime EP1485625B1 (en) 2002-03-20 2002-12-11 Radioisotope generator including one or more component supports

Country Status (24)

Country Link
US (1) US7060998B2 (xx)
EP (1) EP1485625B1 (xx)
JP (1) JP4509575B2 (xx)
KR (1) KR100944839B1 (xx)
CN (1) CN100342145C (xx)
AT (1) ATE466200T1 (xx)
AU (1) AU2002356290B2 (xx)
BR (1) BR0215627B1 (xx)
CA (1) CA2476930C (xx)
CY (1) CY1110674T1 (xx)
DE (2) DE20212683U1 (xx)
DK (1) DK1485625T3 (xx)
ES (1) ES2344633T3 (xx)
GB (1) GB2386742B (xx)
HK (1) HK1056434A1 (xx)
IL (1) IL163438A (xx)
MX (1) MXPA04008839A (xx)
NO (1) NO332227B1 (xx)
NZ (1) NZ534612A (xx)
PT (1) PT1485625E (xx)
RU (1) RU2300673C2 (xx)
SI (1) SI1485625T1 (xx)
WO (1) WO2003081055A1 (xx)
ZA (1) ZA200406503B (xx)

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EP3101659B1 (en) * 2006-10-06 2017-07-26 Mallinckrodt Nuclear Medicine LLC Self-aligning radioisotope elution system
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US8809804B2 (en) * 2011-01-19 2014-08-19 Mallinckrodt Llc Holder and tool for radioisotope elution system
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GB2386742B (en) * 2002-03-20 2004-02-11 Amersham Plc Radioisotope generator component support

Also Published As

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BR0215627A (pt) 2005-03-22
US7060998B2 (en) 2006-06-13
RU2004125148A (ru) 2005-06-10
RU2300673C2 (ru) 2007-06-10
CN1623042A (zh) 2005-06-01
DE20212683U1 (de) 2003-01-16
ZA200406503B (en) 2005-11-30
WO2003081055A1 (en) 2003-10-02
GB2386742A (en) 2003-09-24
KR20040099334A (ko) 2004-11-26
CY1110674T1 (el) 2015-06-10
JP4509575B2 (ja) 2010-07-21
GB0206550D0 (en) 2002-05-01
ES2344633T3 (es) 2010-09-02
US20050104016A1 (en) 2005-05-19
HK1056434A1 (en) 2004-02-13
AU2002356290A1 (en) 2003-10-08
SI1485625T1 (sl) 2010-10-29
MXPA04008839A (es) 2004-11-26
CN100342145C (zh) 2007-10-10
CA2476930C (en) 2010-09-21
GB2386742B (en) 2004-02-11
NZ534612A (en) 2007-01-26
DE60236211D1 (de) 2010-06-10
NO20043928L (no) 2004-09-20
JP2006508300A (ja) 2006-03-09
PT1485625E (pt) 2010-07-26
KR100944839B1 (ko) 2010-03-04
IL163438A (en) 2008-11-26
AU2002356290B2 (en) 2007-09-06
CA2476930A1 (en) 2003-10-02
BR0215627B1 (pt) 2011-04-05
DK1485625T3 (da) 2010-08-09
NO332227B1 (no) 2012-07-30
EP1485625A1 (en) 2004-12-15
ATE466200T1 (de) 2010-05-15

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